Backed by Russian air power, regime forces had managed to fight their way into western Mayadeen on Friday.
"Counter-offensives by IS managed to force the regime fighters away from the western outskirts of Mayadeen," the Britain-based Syrian Observatory for Human Rights said.
Observatory chief Rami Abdel Rahman said the Syrian forces were now some six kilometres (nearly four miles) from the town, which was being targeted by "intensive air strikes carried out by both regime and Russian aircraft".
IS has controlled Mayadeen in Syria's eastern province of Deir Ezzor since 2014.
The town is on the western bank of the Euphrates River, between provincial capital Deir Ezzor, where the militants still hold several districts, and the border with Iraq.
Many of the IS militants who fled an offensive by US-backed forces against the group's de facto Syrian capital Raqa have decamped to the towns of Mayadeen and Albu Kamal in the Euphrates Valley.
The militants are being pressed by twin offensives in eastern Syria: by Russia-backed regime forces and by US-supported Arab-Kurd alliance the Syrian Democratic Forces.